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Background: The early identification of patients' profiles most likely to respond to and maintain long-term therapy with a biological drug can have clinical and cost-effectiveness implications., Objectives: To evaluate the utility of an innovative approach for early identification of patient profiles associated with long-term persistence of golimumab, a tumour necrosis factor inhibitor, in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (SpA) under real-world conditions., Design: Retrospective non-interventional database analysis., Methods: Kaplan-Meier curves of golimumab retention over 8 years from the BIOBADASER registry, overall and by indication, were analysed using a novel approach (a two-phase decay model) to identify the point at which the golimumab retention curve shifted from rapid (indicating high golimumab discontinuation rate) to slow decay (low discontinuation rate). Factors associated with golimumab retention at these time points were identified using Cox regression, and retention rates for different patient profiles were calculated., Results: 885 patients were included. The golimumab retention curve shifted from rapid to slow decay at month 10 for the overall population (retention rate: 73.4%), at month 24 for RA patients (retention: 45.0%), and at month 8 for SpA, including axial SpA and PsA (81.6%). Factors associated with golimumab discontinuation at these early points were, overall, similar to those previously identified at year 8 (RA diagnosis, golimumab as second- or third-line of biological therapy, disease activity over the median and treatment with corticosteroids at golimumab initiation, advanced age [in RA], and female gender [in SpA])., Conclusion: With this novel approach, the factors associated with long-term retention were identified in the initial period of rapid discontinuation of golimumab., Competing Interests: MS-J and LC-C: full-time employee at MSD, Spain. MP-S: consulting honorarium from Janssen and MSD; lectures for Janssen, MSD and Novartis. IC: consulting honorarium from Pfizer and Galapagos; lectures for BMS, GSK, Lilly, Pfizer, MSD and Janssen. FD-G: consulting fees from AbbVie, Lilly, Pfizer, Galapagos; for conferences from Janssen, Galapagos, AbbVie, Novartis; and for financial aid to research from Janssen, Novartis, MSD and AbbVie. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AO declared a shared parent affiliation with the author IC to the handling editor at the time of review., (Copyright © 2024 García-Dorta, González-Dávila, Sánchez-Jareño, Cea-Calvo, Pombo-Suárez, Sánchez-Alonso, Castrejón and Díaz-González.)

Objective: Women with psoriatic arthritis (PsA) may have reduced tumor necrosis factor inhibitor (TNFi) effectiveness compared to men. We examined sex differences in treatment response and retention rates during 24 months of follow-up among patients with PsA initiating their first TNFi., Methods: Data from patients with PsA across 13 European Spondyloarthritis Research Collaboration Network registries starting their first TNFi were pooled. Logistic regression was used to analyze the association between sex and treatment response using low disease activity (LDA) according to the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) (<3.2) at six months as the primary outcome. Analyses were adjusted for age, country, conventional synthetic disease-modifying antirheumatic drug treatment, and TNFi start year. Retention rates were explored using the Kaplan-Meier estimator., Results: We analyzed the treatment response of 7,679 patients with PsA (50% women) with available data on LDA at six months. At baseline, women and men had similar characteristics, including mean DAS28-CRP (women vs men, 4.4 [SD 1.2] vs 4.2 [SD 1.2]), though patient-reported outcome measures were worse in women. At six months, 64% of women and 78% of men had LDA (relative risk [RR] 0.82; 95% confidence interval [CI] 0.80-0.84). This difference was similar after adjustment (RR 0.83; 95% CI 0.81-0.85). TNFi retention rates were evaluated in 17,842 patients with PsA. Women had significantly lower retention rates than men at all time points (women 79%, 64%, and 50% vs men 88%, 77%, and 64% at 6, 12, and 24 months, respectively)., Conclusion: Despite comparable disease characteristics at baseline, women with PsA have reduced treatment response and retention rates to their first TNFi, highlighting the need to consider sex differences in PsA research and management., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: The persistence of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs(DMARDs) in monotherapy versus in combination with conventional synthetic (cs) DMARDs is still a controversial topic in rheumatic diseases. To clarify this issue, the retention of the initial treatment strategy of b/tsDMARD in combination with csDMARD versus monotherapy in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients under real-life conditions was evaluated. Factors associated with maintenance of the initial strategy were analysed., Methods: Nested cohort study within the Spanish BIOBADASER III registry. Bivariate comparisons and multivariate Cox proportional hazards models were used for the analyses., Results: A total of 2521 patients were included in the study. In the multivariate model, the initial strategy of combination therapy was associated with shorter persistence in patients with RA (hazard ratio [HR] 1.58;95% confidence interval [CI] 1.00-2.50; p = .049), PsA (HR 2.48; 95% CI 1.65-3.72) and AS (HR 16.77; 95% CI 7.37-38.16; p < .001), regardless of sex, time of disease progression, baseline disease activity, glucocorticoid use or type of b/tsDMARD. Overall, the combination strategy was associated with an increased incidence of adverse events (incidence rate ratio [IRR] 1.13; 95% CI 1.05-1.21)., Conclusions: In this real-life study, the strategy of combining a b/tsDMARD with a csDMARD is associated with lower persistence and worse safety profile compared to monotherapy in RA and especially in PsA and AS, suggesting that combination therapy should be rethought as first choice in RA patients, but especially in PsA and AS patients., (© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: In patients with rheumatic diseases, the use of biological (b) or targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) after discontinuation of tumor necrosis factor inhibitors (TNFi) is known to be effective. However, data on the use of TNFi after discontinuation of non-TNFi bDMARDs or tsDMARDs (non-TNFi) are scarce. This study assessed the 4-years golimumab retention in patients with rheumatic diseases when used after discontinuation of non-TNFi., Methods: Adults with rheumatoid arthritis (RA; n = 72), psoriatic arthritis (PsA; n = 30) or axial spondyloarthritis (axSpA; n = 23) who initiated golimumab after discontinuation of non-TNFi from the Spanish registry of biological drugs (BIOBADASER) were analyzed retrospectively. The retention rate (drug survival or persistence) of golimumab up to 4 years was evaluated., Results: The golimumab retention rate was 60.7% (51.4-68.8) at year 1, 45.9% (36.0-55.2) at year 2, 39.9% (29.8-49.7) at year 3 and 33.4% (23.0-44.2) at year 4. Retention rates did not differ significantly whether golimumab was used as second, third, or fourth/subsequent line of therapy (p log-rank = 0.462). Golimumab retention rates were higher in axSpA or PsA patients than in RA patients (p log-rank = 0.002). When golimumab was administered as third or fourth/subsequent line, the 4-years retention rate after discontinuation of non-TNFi was similar to that after discontinuation of TNFi., Conclusion: In patients who discontinued non-TNFi, most of whom received golimumab as third/subsequent line of therapy, one-third of patients remained on golimumab at year 4. Retention rates were higher in patients with axSpA and PsA than in those with RA., (© 2023. The Author(s).)

Aim: To assess the golimumab retention rate during up to 8 years of follow up, and any associated factors., Methods: Retrospective analysis of the BIOBADASER (Spanish registry of biological drugs) database, assessing all adults who had ever started golimumab >6 months before the analysis for an approved indication (rheumatoid arthritis [RA], axial spondyloarthritis [SpA] or psoriatic arthritis [PsA])., Results: Among 885 patients (RA 267, axial SpA 370, PsA 248) receiving 944 cycles of golimumab, the retention rate of golimumab was 71.1% (95% confidence interval: 68.0-73.9) at year 1% and 37.7% (95% CI: 33.3-42.1) at year 7 and at year 8. Retention was higher when golimumab was used as the first biological drug (81.7% at year 1, 49.9% at year 7, p < 0.001). In Cox regression analysis, factors associated with golimumab retention included use as first-line therapy (hazard ratio [HR] for discontinuation 1.52 for second- and 1.79 for third/later-line vs. first-line), use in axial SpA or PsA rather than RA (HR for axial SpA vs. RA 0.59, for PsA vs. Rheumatoid arthritis 0.67), and treatment with concomitant methotrexate (HR 0.67). Factors associated with golimumab discontinuation were corticosteroid use (HR 1.46) and disease activity above median (HR 1.29) at golimumab initiation., Conclusion: Based on this retrospective analysis of the BIOBADASER registry, nearly two-fifths (37.7%) of adult rheumatology patients initiating golimumab will remain on treatment for 8 years, with a higher probability of retention in axial SpA or PsA indications and when golimumab is used as first biologic., (© 2022 The Authors. Musculoskeletal Care published by John Wiley & Sons Ltd.)

Introduction and Objectives: Despite the evidence, there are doubts about the positioning of apremilast in the psoriatic arthritis (PsA) treatment algorithm. The objective of this project was to collect the scientific evidence and the experience of a group of rheumatologists who are experts in the management of PsA with apremilast in clinical practice in Spain., Material and Methods: A scientific committee made up of 6 experts proposed 5 clinical scenarios where the evidence on the use of apremilast in PsA was controversial: (i) Efficacy in peripheral PsA; (ii) Efficacy in enthesitis and dactylitis; (iii) Efficacy in PsA with skin involvement; (iv) Comorbidities; and (v) Apremilast safety. After this, a panel of 17 rheumatologists with expertise in PsA management discussed these scenarios and generated a questionnaire with 50 questions and 156 items following the Delphi methodology. This questionnaire was anonymously answered by the panel., Results: After 2 voting rounds, the panel of experts reached consensus in 93 of the 156 items raised (59.6%) (67 in agreement and 26 in disagreement). The degree of consensus was 53.3% in the area of "Efficacy in peripheral PsA"; 60.0% in "Efficacy in enthesitis and dactylitis"; 50.0% in "Efficacy in PsA with skin involvement"; 57.1% in "Management of comorbidities in patients with PsA"; and 67.3% in "Implications of safety in the use of apremilast"., Conclusions: The structured opinion of the experts complements the available evidence and contributes to the establishment of consensual guidelines for the use of apremilast in PsA., (Copyright © 2022 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: The purpose of this study was to compare physical activity (PA) in a group of patients with psoriatic arthritis (PsA) versus healthy controls and to determine whether the mobility of these patients is affected by disease activity., Methods: A group of 52 patients with PsA and 53 controls were included in this case-control study. PA was assessed by accelerometry in both groups and additionally with the International Physical Activity Questionnaire (IPAQ) in patients with PsA. Multiple regression analysis was used to compare PA between groups and to determine the relationship between PA and PsA features, including disease activity, as assessed by the 28-joint Disease Activity Score (DAS28) and the Disease Activity Index for Psoriatic Arthritis (DAPSA) score. In a group of 36 patients, a test-retest study was carried out after 6 months., Results: The time engaged in moderate-to-vigorous physical activity (MVPA) per day, as evaluated by accelerometry, and adjusted by confounders, proved similar in patients with PsA and controls. In patients with PsA, disease activity was inversely related to PA as assessed either by IPAQ or accelerometry. When PA was compared in patients with PsA between the 2 visits, a significant difference in the amount of time doing MVPA was found (42 ± 33 versus 30 ± 22 minutes/day; P = 0.004). Interestingly, in the test-retest study, variations in disease activity over time based on DAPSA scores (r = -0.49, P = 0.002) and DAS28 using the C-reactive protein level (r = -0.4, P = 0.017) were inversely correlated with changes in PA, as determined by accelerometry., Conclusion: Patients with PsA show levels of PA like healthy controls. In patients with PsA, disease activity and PA are inversely correlated and the evaluation of PA by accelerometry is sensitive to changes in disease activity., (© 2020, American College of Rheumatology.)

Background: Retention of biological treatment provides a marker of drug effectiveness and patient satisfaction. Retention of golimumab was high in clinical trial extensions and real-world studies up to 5 years in patients with immune-mediated rheumatic diseases., Objective: To assess the probability of real-world long-term retention of treatment with golimumab up to 7 years after treatment initiation., Methods: This retrospective noninterventional study involved analysis of the Spanish biological drugs registry, BIOBADASER. Adults who had ever received golimumab for rheumatoid arthritis (RA), axial spondyloarthritis (SpA), or psoriatic arthritis (PsA), and had initiated it > 6 months before the analysis date, were included., Results: Among 685 patients (28.5% RA, 42.9% SpA, 28.6% PsA), the overall probability of retention of golimumab treatment since initiation was 71.7% (95% confidence interval 68.1-74.9) at year 1, 60.5% (56.5-64.2%) at year 2, 55.6% (51.5-59.5%) at year 3, 50.6% (46.2-54.8%) at year 4, 45.1% (40.1-50.0%) at year 5, 44.2% (39.0-49.3) at year 6, and 39.5% (32.8-46.2) at year 7. Retention was greater in patients with axial SpA or PsA versus RA (p < 0.001) and when golimumab was used as first-line treatment versus third or later lines (p < 0.001). Factors associated with greater golimumab retention in Cox regression included use as first-line biological therapy, having axial SpA or PsA rather than RA, and concomitant methotrexate therapy. Steroids were associated with lower retention., Conclusion: In this real-world study of RA, axial SpA, and PsA patients, the retention rate of golimumab was 39.5% at year 7. Key Points • Retention of biological treatment provides a marker of drug effectiveness and patient satisfaction. • This real-world study of 685 patients with rheumatoid arthritis (RA), axial spondyloarthritis (SpA), or psoriatic arthritis (PsA) showed that golimumab treatment had a retention rate up to 39.5% at year 7. • Greater golimumab retention was associated with use as first-line biological therapy, having axial SpA or PsA rather than RA, and concomitant methotrexate therapy., (© 2021. International League of Associations for Rheumatology (ILAR).)

The better understanding of the safety of biologic DMARDs (bDMARDs), as well as the emergence of new bDMARDs against different therapeutic targets and biosimilars have likely influenced the use patterns of these compounds over time. The aim of this study is to assess changes in demographic characteristics, disease activity and treatment patterns in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) who started a first- or second-line biologic between 2007 and mid-2020. Patients diagnosed with RA, PsA or AS included in the BIOBADASER registry from January 2007 to July 2020 were included. According to the start date of a first- or second-line biologic therapy, patients were stratified into four time periods: 2007-2009; 2010-2013; 2014-2017; 2018-2020 and analyzed cross-sectionally in each period. Demographic and clinical variables, as well as the type of biologic used, were assessed. Generalized linear models were applied to study the evolution of the variables of interest over time periods, the diagnosis, and the interactions between them. A total of 4543 patients initiated a first biologic during the entire time frame of the study. Over the four time periods, disease evolution at the time of biologic initiation (p < 0.001), disease activity (p < 0.001), retention rate (p < 0.001) and the use of tumor necrosis factor inhibitors as a first-line treatment (p < 0.001) showed a significant tendency to decrease. Conversely, comorbidities, as assessed by the Charlson index (p < 0.001), and the percentage of patients using bDMARDs in monotherapy (p < 0.001), and corticosteroids (p < 0.001) tended to increase over time. Over the entire period of the study's analysis, 3289 patients started a second biologic. The following trends were observed: decreased DAS28 at switching (p < 0.001), lower retention rates (p = 0.004), and incremental changes to the therapeutic target between the first and second biologic (p < 0.001). From 2007 until now rheumatic patients who started a biologic were older, exhibited less clinical activity, presented more comorbidities, and switched to a different biologic more frequently and earlier., (© 2021. The Author(s).)

Objective: The prevalence of psoriatic arthritis (PsA) is very heterogeneous. There are no data on its frequency in the general population in Spain. The aim of EPISER2016 study was to estimate the prevalence of PsA in people aged ≥20 years in Spain., Methods: Cross-sectional multicenter population-based study. Subjects from all the autonomous communities in Spain were randomly selected using multistage stratified cluster sampling. Participants in each of the municipalities randomly selected for the study were administered a telephone-based questionnaire to screen for the study diseases. If the participant reported being previously diagnosed, rheumatologists from the participant's reference hospital confirmed the diagnosis based on a review of the clinical history. Subjects not previously diagnosed but whose screening result was positive based on symptoms received a second telephone call from the investigating rheumatologist in order to evaluate the suspicion. If the suspicion remained, an appointment was made at the reference hospital to complete the diagnostic confirmation process according to CASPAR criteria. To calculate the prevalence and its 95% confidence interval (CI), the sample design was taken into account and weighing was calculated considering age, sex and geographic origin., Results: The sample comprised 4916 subjects. The prevalence of PsA was 0.58% (95%CI: 0.38-0.87). All but 1 of the 27 cases (96.30%) had been diagnosed prior to EPISER2016., Conclusion: The prevalence of PsA in Spain was among the highest reported to date, only below that reported in Norway (0.67%) and slightly higher than that reported in Italy (0.42%)., Competing Interests: EPISER2016 has been funded by Celgene, Gebro Pharma, Merck Sharp & Dohme in Spain, Pfizer and Sanofi-Aventis. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: To assess whether age, at the beginning of biologic treatment, is associated with the time a first adverse event (AE) appears in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA)., Methods: All patients in the BIOBADASER registry diagnosed with RA, AS, and PsA, and classified as young (< 25 years old), adult (25-64 years old), elderly (65-75 years old) or very elderly (> 75 years old) at start of biological treatment were included. Factors associated with the appearance of a first AE using adjusted incidence rate ratios (IRR) (Poisson regression) were analyzed. Survival to first AE was studied by Kaplan-Meier analysis and hazard ratios (HR) by Cox regression., Results: 2483 patients were included: 1126 RA, 680 PsA, and 677 AS. Age group stratification was as follows: 63 young, 2127 adults, 237 elderly, and 56 very elderly. Regression model revealed an increased probability of suffering a first AE at age 65 years or older [IRR elderly: 1.42 (CI95% 1.13-1.77)]. Other characteristics associated with AE were female gender, the use of DMARDs, including methotrexate, the presence of comorbidities, and the time of disease duration. Factors that had the greatest impact on survival over a first AE were age > 75 years [HR 1.50 (1.01-2.24)] and female gender [HR 1.42 (1.22-1.64)]., Conclusion: Age at the start of treatment and female gender are key factors associated with the appearance of a first AE with biologics. Other factors related to patient status and treatment were also associated with a first AE in rheumatic patients treated with biologics.

Objective: Cholesterol efflux capacity (CEC) is the ability of high-density lipoprotein (HDL) cholesterol to accept cholesterol from macrophages. CEC is linked to cardiovascular events in the general population, and it has been shown to be disrupted in inflammatory states. The aim of this study was to establish whether CEC is impaired in PsA patients and if this could be explained by disease-related features like disease activity., Methods: Case-control study that encompassed 105 individuals: 52 PsA patients and 53 controls. CEC, using an in vitro assay, and lipoprotein serum concentrations were assessed in patients and controls. Disease activity in patients with PsA was measured using the Disease Activity Index for Psoriatic Arthritis (DAPSA). Multivariate analysis was performed to study the differences between CEC in patients and controls, and the relation of CEC with PsA activity-related data and lipid profile., Results: Total cholesterol, apolipoprotein A1, and LDL cholesterol serum levels were downregulated in PsA patients. CEC did not differ between controls and patients (17 ± 10 vs. 18 ± 2%, p = 0.15) after adjusting for traditional cardiovascular risk factors or other variations in the lipid profile related to the disease. Traditional cardiovascular risk factors, both in patients and controls, were not related to CEC. After multivariate regression analysis, the DAPSA score was inversely and independently associated with CEC (beta coefficient - 0.75 [95%CI - 1.39-- 0.11] %, p = 0.023)., Conclusion: CEC is inversely associated with disease activity in PSA patients, reinforcing the role of disease activity as a key factor in the development of accelerated atherosclerosis in these patients.Key Points• Cholesterol efflux capacity is linked to cardiovascular events in the general population.• In patients with psoriatic arthritis, cholesterol efflux capacity is inversely associated with disease activity (beta coefficient - 0.75[95% CI - 1.39-- 0.11] %, p = 0.023).• This finding reinforces the role of disease activity as a key factor in increasing cardiovascular risk in psoriatic arthritis patients.

Objective: Apremilast, an oral phosphodiesterase 4 inhibitor, downregulates intracellular inflammatory mediator synthesis by elevating cyclic adenosine monophosphate levels. The PALACE 2 trial evaluated apremilast efficacy and safety in patients with active psoriatic arthritis (PsA) despite prior conventional disease-modifying antirheumatic drugs and/or biologic therapy., Methods: Eligible patients were randomized (1:1:1) to placebo, apremilast 20 mg BID, or apremilast 30 mg BID. At Week 16, patients with swollen and tender joint count improvement < 20% entered early escape, with placebo patients rerandomized (1:1) to apremilast 20 mg BID or 30 mg BID while apremilast patients continued on their initial apremilast dose. At Week 24, patients remaining on placebo were rerandomized to apremilast 20 mg BID or 30 mg BID. The primary endpoint was the proportion of patients achieving > 20% improvement in American College of Rheumatology response criteria (ACR20) at Week 16., Results: In the intent-to-treat population (N = 484), ACR20 at Week 16 was achieved by more patients receiving apremilast 20 mg BID [37.4% (p = 0.0002)] and 30 mg BID [32.1% (p = 0.0060)] versus placebo (18.9%). Clinically meaningful improvements in signs and symptoms of PsA, physical function, and psoriasis were observed with apremilast through Week 52. The most common adverse events were diarrhea, nausea, headache, and upper respiratory tract infection. Diarrhea and nausea generally occurred early and usually resolved spontaneously with continued treatment. Laboratory abnormalities were infrequent and transient., Conclusion: Apremilast demonstrated clinical improvements in PsA for up to 52 weeks, including signs and symptoms, physical function, and psoriasis. No new safety signals were observed. ClinicalTrials.gov identifier: NCT01212757.

Objective: To study the qualitative and quantitative phenotypic changes that occur in molecules involved in antigen presentation and costimulation in synovial B cells from rheumatoid arthritis (RA) and psoriatic arthritis (PsA)., Methods: The presence of HLA-DR, CD86, and CD40 in CD20+ cells was studied in RA synovium biopsies using immunohistochemistry and immunofluorescence. Expression was assessed by flow cytometry of the Class II molecules CD40, CD86, CD23, and CD27 on B cells from the synovial fluid (SF), with respect to peripheral blood, from 13 patients with RA and 15 patients with PsA. Expression of interferon-induced protein with tetratricopeptide repeats 4 (IFIT4) in immune-selected CD20+ cells from patients with RA was assessed by quantitative realtime PCR., Results: Infiltrating synovial RA, B cells expressed HLA-DR, CD40, and CD86. Increased expression of CD86, HLA-DR, and HLA-DQ in B cells from SF was found in patients with RA and PsA. HLA-DP was also elevated in rheumatoid SF B cells; conversely, a significantly lower expression was observed in SF from patients with PsA. CD40 expression was increased in SF B cells from PsA, but not in patients with RA. Interestingly, CD20 surface expression level was significantly lower in SF B cells (CD19+, CD138-) from RA, but not in patients with PsA. CD27 upregulation and CD23 downregulation were observed in synovial B cells in both pathologies. Finally, a 4-fold increase in IFIT4 mRNA content was shown in B cells from SF in patients with RA., Conclusion: Synovial B cells from patients with RA and patients with PsA express different antigen-presenting cell phenotypes, suggesting that this cell type plays a dissimilar role in the pathogenesis of each disease.